Project Summary/Abstract Biological imaging is a vital technology in modern cancer and cell biological research and remains an essential component of all research programs at the Fox Chase Cancer Center (FCCC). This shared instrument grant application requests for funds to purchase a multiphoton photon microscope (MPM) imaging system. The MPM will be a new addition to the Core supported Biological Imaging Facility (BIF) at the FCCC. The mission of this core facility is to provide cost-effective access state-of-the-art equipment and technologies to its research base. Users within the Fox Chase Cancer Center and Temple University faculty who are members of the Cancer Center have access to a full range of light and electron microscopy equipment, and various small animal imaging modalities. For our 2015 Core grant renewal application, we listed 52 investigators who used and acknowledged the BIF in their publications. The BIF received an excellent to outstanding score from the Core grant reviewers. This Facility continually expands its capabilities to its users by adopting new imaging technologies and equipment. Multiphoton microscopy will provide users ability: 1) for deep penetration imaging of cells in tissues of live animals and explants; 2) imaging tumor microenvironment (including stromal fibroblasts, infiltrating immune and inflammatory cells, blood and lymphatic vascular network, and the extracellular matrix) using SHG; 3) high-speed, low photobleaching real-time 3D imaging of model systems. The shared equipment requested in this application is an important and necessary addition to the broad suite of imaging equipment currently available to users of the BIF and it will have fundamental and significant impact on PHS funded research at the FCCC. Our need for MPM imaging came from increasing requests by investigators whose research programs depend on this technology. Accessibility of a shared MPM by our investigators will therefore significantly enhance their research efforts. In addition, the availability of MPM technology will enhance the ability of FCCC to recruit new investigators who may have a critical need for this technology in their research programs. As with all of the high-end imaging instruments in the BIF, the MPM is not affordable to purchase and maintain by any individual lab. It is therefore highly suited as a shared instrument in a facility that is partly funded by the NCI Core grant mechanism. The BIF has over 20 years of experience in providing users access to shared high-resolution imaging solutions and are thus qualified to operate, manage and maintain the MPM.